Avian influenza vaccines and methods of making same

Abstract

The disclosure relates to avian influenza vaccines produced through reverse genetics to protect from A/Turkey/Indiana/22-like virus, methods for producing such vaccines, and method for using such vaccines to protect poultry. The disclosure also relates to methods of producing influenza viruses comprising chimeric polynucleotides having an HA non-coding sequence from an apathogenic high growth influenza virus and a polynucleotide encoding an HA protein from a highly pathogenic avian influenza virus or variant thereof, and/or having a chimeric polynucleotide having an NA non-coding sequence from an apathogenic high growth influenza virus and a polynucleotide encoding an NA protein from a highly pathogenic avian influenza virus or variant thereof.

We claim: 
     
         1 . A chimeric polynucleotide comprising:
 a hemagglutinin (HA) non-coding sequence from an apathogenic high growth influenza virus and a polynucleotide encoding an HA protein from a highly pathogenic avian influenza virus or a variant thereof, or   a neuraminidase (NA) non-coding sequence from an apathogenic high growth influenza virus and a polynucleotide encoding an NA protein from a highly pathogenic avian influenza virus or a variant thereof.   
     
     
         2 . The chimeric polynucleotide of  claim 1 , wherein the apathogenic high growth influenza virus is A/PuertoRico/8/34 (PR8). 
     
     
         3 . The chimeric polynucleotide of  claim 1 , wherein the polynucleotide encoding the HA protein encodes an attenuated HA protein. 
     
     
         4 . The chimeric polynucleotide of  claim 3 , wherein the polynucleotide encoding the HA protein encodes an attenuated A/turkey/Indiana/22-003707-003/2022 HA protein or a variant thereof. 
     
     
         5 . The chimeric polynucleotide of  claim 1 , wherein the polynucleotide encoding the NA protein is an N1, N2, N3, N4, N5, N6, N7, N8, or N9. 
     
     
         6 . The chimeric polynucleotide of  claim 1 , wherein the NA protein is from A/turkey/Indiana/22-003707-003/2022, A/Blue Winged Teal/Wyoming/AH0099021/2016, or a variant thereof. 
     
     
         7 . A vector comprising a chimeric polynucleotide of  claim 1 . 
     
     
         8 . The vector of  claim 7 , wherein the vector is a plasmid, a cosmid, a phage, a virus, or a fragment of a virus. 
     
     
         9 . A cell comprising the vector of  claim 7 . 
     
     
         10 . A rescued influenza virus comprising polynucleotides encoding M1/M2, NP, PB1, PA, PB2, and NS1/NS2 from an apathogenic high growth influenza A virus, a polynucleotide encoding an attenuated HA from a high highly pathogenic avian influenza virus, and a polynucleotide encoding an N1, N2, N3, N4, N5, N6, N7, N8, or N9 NA. 
     
     
         11 . The rescued influenza virus from  claim 10 , wherein the polynucleotide encoding HA encodes an attenuated A/turkey/Indiana/22-003707-003/2022 HA or a variant having 90% identity thereto. 
     
     
         12 . The rescued influenza virus from  claim 10 , wherein the polynucleotide encoding NA is from A/turkey/Indiana/22-003707-003/2022, A/Blue Winged Teal/Wyoming/AH0099021/2016, or a variant thereof. 
     
     
         13 . The rescued influenza virus of  claim 12 , wherein the polynucleotide encoding NA is from A/turkey/Indiana/22-003707-003/2022 or a variant thereof. 
     
     
         14 . The rescued influenza virus of  claim 12 , wherein the polynucleotide encoding NA is from A/Blue Winged Teal/Wyoming/AH0099021/2016 or a variant thereof. 
     
     
         15 . The rescued influenza virus of  claim 10 , wherein the polynucleotides encoding M1/M2, NP, PB1, PA, PB2, and NS1/NS2 influenza A are from PR8. 
     
     
         16 . A vector comprising any one of the polynucleotides of  claim 10 . 
     
     
         17 . An immunogenic composition comprising an immunologically-effective amount of the rescued influenza virus of  claim 10 . 
     
     
         18 . A method of producing an influenza virus, the method comprising introducing into a population of host cells a plurality of vectors comprising polynucleotides corresponding to at least six internal segments of an apathogenic high growth influenza virus, a chimeric polynucleotide comprising an HA non-coding sequence from an apathogenic high growth influenza virus and a polynucleotide encoding an attenuated HA protein from a highly pathogenic avian influenza virus or a variant thereof, and a chimeric polynucleotide comprising an NA non-coding sequence from an apathogenic high growth influenza virus and a polynucleotide encoding an NA protein from a highly pathogenic avian influenza virus or a variant thereof, culturing the population of host cells at a temperature that is less or equal to about 35° C., and recovering the virus. 
     
     
         19 . The method of  claim 18 , wherein the apathogenic virus is PR8, the HA is from A/turkey/Indiana/22-003707-003/2022 or a variant thereof, and the NA is N1, N2, N3, N4, N5, N6, N7, N8, or N9. 
     
     
         20 . The method of  claim 18 , wherein the NA is from A/turkey/Indiana/22-003707-003/2022, A/Blue Winged Teal/Wyoming/AH0099021/2016, or a variant thereof. 
     
     
         21 . A method of producing an influenza virus, the method comprising introducing into a population of host cells a plurality of vectors comprising polynucleotides corresponding to at least six internal segments of an apathogenic high growth influenza virus, a polynucleotide encoding an attenuated A/turkey/Indiana/22-003707-003/2022 HA or a variant thereof, and an NA polynucleotide of N1, N2, N3, N4, N5, N6, N7, N8, or N9, culturing the population of host cells at a temperature that is less or equal to 35° C., and recovering the virus. 
     
     
         22 . The method of  claim 21 , wherein the apathogenic virus is PR8. 
     
     
         23 . The method of  claim 21 , wherein the NA polynucleotide is from A/turkey/Indiana/22-003707-003/2022, A/Blue Winged Teal/Wyoming/AH0099021/2016, or a variant thereof.